Christian Medical College, Vellore
Wayne State University, Detroit, USA
Christian Medical College, Vellore
I began my medical career in 1994, after completing the medical education (MBBS) at Christian Medical College, Vellore. My interest in research and clinical medicine was kindled as a junior doctor at a small primary care hospital, when faced with a set of patients with an undifferentiated acute febrile illness, which was later confirmed to be Leptospirosis. As a young doctor sensitized with these experiences, I chose Internal Medicine for post-graduate specialization at my alma mater. It was during my postgraduate training that I was once again challenged with the problem of patients suffering and many dying of an undifferentiated febrile illness of an unclear etiology that adversely affected multiple organ systems. A carefully designed study revealed that these patients had been suffering from scrub typhus, a Rickettsial illness long forgotten in India, with the last report of it published decades earlier. This work established the re-emergence of scrub typhus in India, with the first publication in the Annals of New York Academy of Sciences in 2003. A realization of the profound morbidity and mortality that infections still cause for millions in India, coupled with my love of research especially in the areas of Infectious Diseases and Tropical Medicine, led me to specialize in Infectious Diseases. I received training in Tropical Medicine at the London School of Hygiene & Tropical Medicine followed by training in Infectious Diseases at Wayne State University in the USA, where I obtained a strong foundation in laboratory research apart from clinical expertise. After completing my specialty training, I returned to India, determined to delineate various aspects of scrub typhus. I obtained a grant from the International Society for Infectious Diseases to evaluate the clinical and laboratory manifestations, genetic variability, and outcomes of scrub typhus in Southern India. Besides defining the clinical and laboratory manifestations and outcomes of this infection, I also established genotypes of the causative organism, showing for the first time that Karp-like and Kato-like strains of Orientia tsutsugamushi circulated in South India.
Finding that the commonly used method of testing, nested-PCR, took double the time of conventional PCR and carried an increased risk of contamination during the transfer steps, my laboratory optimized and standardized an earlier described conventional PCR targeting the 56-KDa Type Specific Antigen (TSA). This method was found to be as sensitive and specific as the nested-PCR. Subsequently, I completed an ICMR-funded study characterizing the molecular epidemiology and genetic diversity of Orientia tsutsugamushi from different parts of India. The 56kDa TSA sequences of strains from India were compared to the ones from other parts of Asia and a 10-20% nucleotide variation was observed and this was published in Emerging Infectious Diseases.
Additionally, in collaboration with our partners at the University of Oslo, Norway, I studied the underlying host immunological and inflammatory process during scrub typhus. These studies looked at a wide range of inflammatory mediators in a large population of scrub typhus patients, as compared to controls, using microarray, luminex-based multiplex cytokine assays, and Enzyme immune-assays, and led to the defining of specific chemokine profiles associated with higher-level severity and mortality in this disease. Investigating host susceptibility to scrub typhus and looking at SNPs in TLR4, TLR2, and Heat HSP-70 genes in scrub typhus patients and controls, we also examined a possible association of a mutation with susceptibility to scrub typhus, revealing a significant correlation between the presence of heterozygous TLR4 Asp299Gly polymorphism and scrub typhus infection.
I have always been fascinated by making a difference by doing relevant research. My research straddles the divide between clinical and basic sciences. I have been thrilled by the improvement in outcome of patients with scrub typhus admitted to our institution over the years as demonstrated by halving the case fatality rate. Being a clinician scientist, I firmly believe that the key to progress in the fight against infections in India is by addressing the problems of the population or the society grounded firmly on rapidly growing science by taking it to the cellular or molecular level. In my pursuit, I have been humbled and deeply encouraged by several recognitions such as Guerrant International Young Investigator Award by Infectious Disease Society of America, MG Alexander Award in Tropical Medicine by Clinical Infectious Diseases Society and Linnaeus-Palme Visiting Professor by Swedish Government for the pioneering work in Rickettsial infections. Apart from these recognitions, I have also been conferred with Fellow of Infectious Diseases Society of America and Fellow of Royal College of Physicians.
Currently, we are working on improving the diagnostics for scrub typhus and developing new diagnostics. We have also established collaboration and network with the scientists at Wellcome Trust Units in Thailand and Laos working in the area of Rickettsial infections. I realized there is huge potential and opportunity for world class and world changing research between India and South-East Asia as we share many of the same infectious diseases. Drawing strength from the impact of my research on scrub typhus thus far, I would like to further improve the outcome of this infection focusing on severe disease. The proposed project is aimed to bridge some of the important gaps in knowledge in managing severe scrub typhus. I hope to be able to integrate the new knowledge and experiences I gain into the current framework of my research and build, through interactions with other leading infectious diseases experts, a strong collaborative network that may serve as a future consortium in shaping regional drug policy for scrub typhus.